A straightforward synthesis of 5'-peptide oligonucleotide conjugates using N(alpha)-Fmoc-protected amino acids.

[reaction: see text] 5'-Peptide oligonucleotide conjugates were prepared stepwise on a single support using N(alpha)-Fmoc-protected amino acids and unprotected phosphate groups. The method uses commercially available reagents and is successful with most natural amino acids. The simplicity of the method may encourage researchers to prepare new oligonucleotide-peptide conjugates with novel properties.